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However, the asymmetric synthesis of such heterocycles is limited to the use of transition metal catalysts or chiral phosphoric acids. In the current work, imine reductases (IREDs) are utilized to develop a general biocatalytic method for the stereodivergent synthesis of 5\u2010substituted tetrahydro\u20101,4\u2010benzoxazepines, 4\u2010substituted tetrahydro\u20101,5\u2010benzothiazepines, and 2,2,4\u2010trisubstituted tetrahydro\u20101,5\u2010benzodiazepines in excellent yields (up to 96\u2009%), enantiomeric excess (up to &gt;99\u2009%) and diastereoselectivity (up to &gt;99\u2009%). In addition, imine reductase assisted reductive amination gave facile access to 2,4\u2010disubstituted tetrahydro\u20101,5\u2010benzodiazepines starting from 1,3\u2010diketone and 1,2\u2010diamino benzene with excellent stereoselectivity and high yields. The absolute configuration of the newly synthesized N\u2010heterocycles was determined using vibrational circular dichroism (VCD). The presented methodology has further broadened the scope of IREDs towards the preparation of chiral seven\u2010membered N\u2010heterocycles containing another heteroatom.<\/jats:p>","DOI":"10.1002\/chem.202404537","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T04:54:37Z","timestamp":1739249677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Biocatalytic Stereodivergent Synthesis of Substituted Tetrahydro\u2010Benzo\u2010(Oxa, Thia, and Di)\u2010Azepines"],"prefix":"10.1002","volume":"31","author":[{"given":"Tanaya","family":"Manna","sequence":"first","affiliation":[{"name":"Department of Biological and Synthetic Chemistry Centre of Biomedical Research Sanjay Gandhi Postgraduate Institute of Medical Sciences Campus  Raebareli Road Lucknow 226014 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